XRCC1 protects cells from chromate-induced chromosome damage, but does not affect cytotoxicity

Grlickova-Duzevik, Eliza; Wise, Sandra S.; Munroe, Ray C.; Thompson, W. Douglas; Wise, John Pierce

doi:10.1016/j.mrgentox.2006.06.010

Cited by 12 publications

(6 citation statements)

References 22 publications

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“…These data suggest that medaka cells may also predict the genotoxic response of human cells. By contrast, our medaka data differ from previous reports of Cr(VI) genotoxicity in Chinese hamster ovary (CHO) cells as 1 μM sodium chromate for 24 h damaged 8% of metaphases in CHO cells (Grlickova-Duzevik et al, 2006.). This observation is interesting, as CHO cells are currently used as a standard tool by regulatory agencies to predict human response.…”

Section: Discussioncontrasting

confidence: 99%

Medaka (Oryzias latipes) as a sentinel species for aquatic animals: Medaka cells exhibit a similar genotoxic response as North Atlantic right whale cells

Wise

Goodale

et al. 2009

Comparative Biochemistry and Physiology Part C: Toxicology &

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Hexavalent chromium (Cr(VI)) is emerging as a major concern for aquatic environments, particularly marine environments. Medaka (Oryzias latipes) has been used as a model species for human and aquatic health, including the marine environment, though few studies have directly compared toxicological responses in medaka to humans or other aquatic species. We used a medaka fin cell line to compare the genotoxic response of medaka to Cr(VI) to the response observed in North Atlantic right whale cells to see if responses in medaka were similar to those of other aquatic species, particularly aquatic mammals. We used the production of chromosomal aberrations as a measure of genotoxicity. We found that in medaka cells, concentrations of 1, 5 and 10 μM sodium chromate damaged 17, 32 and 43% of metaphases, respectively and these same concentrations 1, 2.5, 5 and 10 μM sodium chromate damaged 14, 24 and 49% of metaphases, respectively, in North Atlantic right whale lung cells and 11, 32 and 41% of metaphases, respectively, in North Atlantic right whale testes cells. These data show that genotoxic responses in medaka are comparable to those seen in North Atlantic right whale cells, consistent with the hypothesis that medaka are a useful model for other aquatic species.

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Section: Discussioncontrasting

confidence: 99%

Medaka (Oryzias latipes) as a sentinel species for aquatic animals: Medaka cells exhibit a similar genotoxic response as North Atlantic right whale cells

Wise

Goodale

et al. 2009

Comparative Biochemistry and Physiology Part C: Toxicology &

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“…The work by Sugden et al (7,8) has demonstrated that, in addition to guanine, 8-oxoguanine is further oxidized by a Cr(V)-containing compound. Interestingly, EM9 CHO cells (X-ray cross-complementing group 1 (XRCC1) deficient) are hypersensitive toward clastogenesis by particulate lead chromate, a particulate form of Cr(VI) (38). Because XRCC1 is involved in the resolution of DNA single-strand breaks (SSBs), which are generated by Cr(VI) exposure (39), our results collectively suggest that SSBs, but not Cr(VI)-induced base damage, are preclastogenic lesions.…”

Section: Discussionmentioning

confidence: 71%

Excision repair is required for genotoxin-induced mutagenesis in mammalian cells

Brooks¹,

O’Brien²,

Ceryak³

et al. 2008

Carcinogenesis

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Certain hexavalent chromium [Cr(VI)] compounds are human lung carcinogens. Although much is known about Cr-induced DNA damage, very little is known about mechanisms of Cr(VI) mutagenesis and the role that DNA repair plays in this process. Our goal was to investigate the role of excision repair (ER) pathways in Cr(VI)-mediated mutagenesis in mammalian cells. Repair-proficient Chinese hamster ovary cells (AA8), nucleotide excision repair (NER)-deficient (UV-5) and base excision repair (BER)-inhibited cells were treated with Cr(VI) and monitored for forward mutation frequency at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus. BER was inhibited using methoxyamine hydrochloride (Mx), which binds to apurinic/apyrimidinic sites generated during BER. Notably, we found that both NER-deficient (UV-5 and UV-41) and BER-inhibited (AA8 + Mx) cells displayed attenuated Cr(VI) mutagenesis. To determine whether this was unique to Cr(VI), we included the alkylating agent, methylmethane sulfonate (MMS) and ultraviolet (UV) radiation (260 nm) in our studies. Similar to Cr(VI), UV-5 cells exhibited a marked attenuation of MMS mutagenesis, but were hypermutagenic following UV exposure. Moreover, UV-5 cells expressing human xeroderma pigmentosum complementation group D displayed similar sensitivity to Cr(VI) and MMS-induced mutagenesis as AA8 controls, indicating that the genetic loss of NER was responsible for attenuated mutagenesis. Interestingly, Cr(VI)-induced clastogenesis was also attenuated in NER-deficient and BER-inhibited cells. Taken together, our results suggest that NER and BER are required for Cr(VI) and MMS-induced genomic instability. We postulate that, in the absence of ER, DNA damage is channeled into an error-free system of DNA repair or damage tolerance.

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“…Determination of chromosomal damage was measured as previously described [32][33]. Briefly, logarithmically growing cells were treated with lead chromate for 24 h. Cells were then harvested, resuspended in hypotonic solution and fixed with Carnoy's fixative, dropped onto slides, stained with Giemsa, and cover slips were added.…”

Section: Chromosome Preparationsmentioning

confidence: 99%

“…Briefly, logarithmically growing cells were treated with lead chromate for 24 h. Cells were then harvested, resuspended in hypotonic solution and fixed with Carnoy's fixative, dropped onto slides, stained with Giemsa, and cover slips were added. Background damage levels were subtracted from each data point as previously described [32][33]. Chromosomes were analyzed using our published methods [8].…”

Section: Chromosome Preparationsmentioning

confidence: 99%

Homologous recombination repair protects against particulate chromate-induced chromosome instability in Chinese hamster cells

Stackpole

Wise

Goodale

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Particulate hexavalent chromium [Cr(VI)] compounds are well-established human carcinogens. Cr (VI)-induced tumors are characterized by chromosomal instability (CIN); however, the mechanisms of this effect are unknown. We investigated the hypothesis that homologous recombination (HR) repair of DNA double strand breaks protect cells from Cr(VI)-induced CIN by focusing on the XRCC3 and RAD51C genes, which play an important role in cellular resistance to DNA double strand breaks. We used Chinese hamster cells defective in each HR gene (irs3 for RAD51C and irs1SF for XRCC3) and compared with their wildtype parental and cDNA-complemented controls. We found that the intracellular Cr ion levels varied among the cell lines after particulate chromate treatment. Importantly, accounting for differences in Cr ion levels, we discovered that XRCC3 and RAD51C cells treated with lead chromate had increased cytotoxicity and chromosomal aberrations, relative to wild-type and cDNA-complimented cells. We also observed the emergence of high levels of chromatid exchanges in the two mutant cell lines. For example, 1 ug/cm 2 lead chromate induced 20 and 32 exchanges in XRCC3-and RAD51C-deficient cells, respectively, whereas no exchanges were detected in the wildtype and cDNA-complemented cells. These observations suggest that HR protects cells from Cr(VI)-induced CIN, consistent with the ability of particulate Cr(VI) to induce double strand breaks.

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XRCC1 protects cells from chromate-induced chromosome damage, but does not affect cytotoxicity

Cited by 12 publications

References 22 publications

Medaka (Oryzias latipes) as a sentinel species for aquatic animals: Medaka cells exhibit a similar genotoxic response as North Atlantic right whale cells

Medaka (Oryzias latipes) as a sentinel species for aquatic animals: Medaka cells exhibit a similar genotoxic response as North Atlantic right whale cells

Excision repair is required for genotoxin-induced mutagenesis in mammalian cells

Homologous recombination repair protects against particulate chromate-induced chromosome instability in Chinese hamster cells

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